What are the considerations for using sofosbuvir (Sofosbuvir)-based therapy in patients with Chronic Kidney Disease (CKD) stage 5 on hemodialysis?

Sofosbuvir-Based Therapy in CKD Stage 5 on Hemodialysis

Glecaprevir/pibrentasvir is the preferred first-line treatment for HCV-infected patients with CKD stage 5 on hemodialysis, but sofosbuvir/velpatasvir can be used safely and effectively when no other relevant treatment options are available. 1

Treatment Hierarchy

First-Line: Glecaprevir/Pibrentasvir

• This is the treatment of choice for CKD stage 4-5 including hemodialysis patients 1
• Achieves 98-99% SVR12 rates across all HCV genotypes (1-6) in this population 1
• No dose adjustment required 1
• Proven efficacy: EXPEDITION-4 trial showed 98% SVR12 (102/104 patients) with CKD stage 4-5 1
• Japanese multicenter study demonstrated 99% SVR in hemodialysis patients (99/100) 1

Second-Line: Sofosbuvir-Based Regimens

When to Use:

• When glecaprevir/pibrentasvir is unavailable or contraindicated 1
• For decompensated cirrhosis (Child-Pugh B/C) where protease inhibitors are contraindicated 1

Sofosbuvir/Velpatasvir Specifics:

• Can be used with no dose adjustment despite limited safety data 1, 2
• GS-331007 (sofosbuvir metabolite) exposure increases 20-fold in hemodialysis patients, exceeding levels where adverse reactions occurred in preclinical trials 1
• Despite this accumulation, a 12-week study of 59 hemodialysis patients showed adverse event and death rates were not higher than expected 1
• Multiple real-world studies confirm safety and efficacy 1, 3, 4

Critical Safety Considerations

Renal Pharmacokinetics

• Sofosbuvir is eliminated primarily by renal route 1, 2
• In ESRD patients, sofosbuvir AUC increases 28-60% and GS-331007 AUC increases 1280-2070% depending on dialysis timing 2
• Hemodialysis removes only approximately 18% of administered dose 2
• Despite accumulation, full-dose sofosbuvir (400 mg daily) has been used safely 5, 3, 6, 4

Monitoring Requirements

• Treat in expert centers with multidisciplinary team monitoring 1
• Monitor serum potassium closely—recurrent hyperkalemia occurs in approximately 30% of patients (10/33 in one study) 7
• Check potassium every 4 weeks or on demand during treatment 7
• Monitor renal function and electrolytes, particularly if severe gastrointestinal symptoms develop 7
• No clinically meaningful changes in eGFR or serum creatinine have been reported post-treatment 4

Cardiovascular Safety

• No increased risk for cardiac adverse events has been demonstrated in real-world practice 3
• Adverse event rates comparable to expected baseline in ESRD population 1

Dosing Strategies

Full-Dose Approach (Preferred)

• Sofosbuvir 400 mg once daily with NS5A inhibitor (daclatasvir or ledipasvir) for 12 weeks 5, 6
• Achieves 100% SVR12 in multiple studies 5, 6
• Meta-analysis shows no significant difference in SVR12 (97.1% vs 96.2%, p=0.72) or SAE rate (8.8% vs 2.9%, p=0.13) between full and reduced doses 4

Reduced-Dose Approach (Alternative)

• Some centers use sofosbuvir 200 mg or 3 times weekly 6, 4
• Two relapses occurred with 3-times-weekly regimen vs. none with daily dosing in one study 6
• Daily dosing is recommended over intermittent dosing 6

Ribavirin Considerations

• Avoid ribavirin in severe renal impairment (eGFR <30 mL/min/1.73 m²) 1
• If used, dose at 200 mg/day only if hemoglobin >10 g/dL at baseline 1
• Requires frequent hemoglobin monitoring; interrupt if hemoglobin <8.5 g/dL 1
• Erythropoietin and blood transfusion may be necessary 1
• When ribavirin cannot be used, extend treatment to 24 weeks 1

Alternative Regimens for Specific Genotypes

Genotype 1b

• Grazoprevir/elbasvir for 12 weeks without ribavirin achieves 92-94% SVR12 1
• C-SURFER trial: 92% SVR12 (54/59) in CKD stage 4-5 patients 1

Genotype 1a

• Grazoprevir/elbasvir with ribavirin 200 mg daily (if hemoglobin >10 g/dL) 1
• Ritonavir-boosted paritaprevir/ombitasvir/dasabuvir with ribavirin 200 mg daily 1

Timing of Treatment

Pre- vs. Post-Transplant Decision Algorithm

• Treat all hemodialysis patients who are transplant candidates 1
• HCV-associated liver damage accelerates with immunosuppression 1
• Consider: donor type (living vs. deceased), waiting list times, center policies on HCV-positive donors, HCV genotype, and liver fibrosis severity 1
• If receiving kidney from HCV RNA-positive donor increases transplant likelihood, transplant first and treat HCV post-transplant 1
• High efficacy and safety demonstrated in kidney transplant recipients 1

Common Pitfalls to Avoid

1. Do not withhold sofosbuvir-based therapy solely due to ESRD—multiple studies confirm safety when glecaprevir/pibrentasvir unavailable 1, 3, 4
2. Do not use reduced-dose sofosbuvir intermittently (3 times weekly)—higher relapse rates observed 6
3. Do not add ribavirin routinely in ESRD—high risk of severe anemia 1
4. Do not use protease inhibitors in decompensated cirrhosis with CKD—contraindicated 1
5. Do not neglect potassium monitoring—hyperkalemia recurrence is common 7

Evidence Quality Note

The 2020 EASL guidelines represent the most recent high-quality evidence, superseding the 2017 recommendations that advised caution with sofosbuvir in severe renal impairment 1. The updated guidance reflects accumulating real-world data demonstrating safety and efficacy 3, 4. The FDA label acknowledges limited safety data but permits use when no other options available 2.